Autism spectrum disorders (ASDs) are neurodevelopmental syndromes characterised by repetitive behaviours and restricted interests, impairments in social behaviour and relations, and in language and ...communication. These symptoms are also observed in a number of developmental disorders of known origin, including Fragile X Syndrome, Rett Syndrome, and Foetal Anticonvulsant Syndrome. While these conditions have diverse etiologies, and poorly understood pathologies, emerging evidence suggests that they may all be linked to dysfunction in particular aspects of GABAergic inhibitory signalling in the brain. We review evidence from genetics, molecular neurobiology and systems neuroscience relating to the role of GABA in these conditions. We conclude by discussing how these deficits may relate to the specific symptoms observed.
Sensory processing abnormalities are common in autism spectrum disorders (ASD), and now form part of the Diagnostic and Statistical Manual 5th Edition (DSM-5) diagnostic criteria, but it is unclear ...whether they characterize the ‘broader phenotype’ of the disorder. We recruited adults (
n
= 772) with and without an ASD and administered the Autism Quotient (AQ) along with the Adult/Adolescent Sensory Profile (AASP), the Cardiff Anomalous Perceptions Scale (CAPS), and the Glasgow Sensory Questionnaire (GSQ), all questionnaire measures of abnormal sensory responsivity. Autism traits were significantly correlated with scores on all three sensory scales (AQ/GSQ
r
= 0.478; AQ/AASP
r
= 0.344; AQ/CAPS
r
= 0.333; all
p
< 0.001). This relationship was linear across the whole range of AQ scores and was true both in those with, and without, an ASD diagnosis. It survived correction for anxiety trait scores, and other potential confounds such as mental illness and migraine.
Recent studies point to overlap between neuropsychiatric disorders in symptomatology and genetic aetiology.
To systematically investigate genomics overlap between childhood and adult ...attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD).
Analysis of whole-genome blood gene expression and genetic risk scores of 318 individuals. Participants included individuals affected with adult ADHD (n = 93), childhood ADHD (n = 17), MDD (n = 63), ASD (n = 51), childhood dual diagnosis of ADHD-ASD (n = 16) and healthy controls (n = 78).
Weighted gene co-expression analysis results reveal disorder-specific signatures for childhood ADHD and MDD, and also highlight two immune-related gene co-expression modules correlating inversely with MDD and adult ADHD disease status. We find no significant relationship between polygenic risk scores and gene expression signatures.
Our results reveal disorder overlap and specificity at the genetic and gene expression level. They suggest new pathways contributing to distinct pathophysiology in psychiatric disorders and shed light on potential shared genomic risk factors.
There are substantial health inequalities for seasonal agricultural workers and their families in the United States. One identified inequality is in health literacy. The authors explored the ...implementation and impact of connecting youth from seasonal farmworker families who participated in a leadership and college pipeline program with Internet access by providing a tablet with a paid cellular data plan and university library-based health literacy training.
With the support of a National Network of Libraries of Medicine Health Information Outreach Award, we conducted a qualitative, utilization-focused evaluation by conducting semi-structured interviews from December 2017 through February 2018 with middle and high school age participants in the program (n=10). After parental consent and youth assent, we recorded interviews with participants at program activity locations or in their homes. We then utilized inductive thematic analysis with 2 primary coders.
We identified four themes: (1) having access to the Internet can be transformative, (2) access resulted in increased knowledge of and interest in one's own and others' health, (3) "Google" is the norm, and (4) participant training increased self-efficacy to determine credible sources and resources.
Providing Internet access and iPads was possible to implement and resulted in increased utilization of health information. The combination of Internet access with training on information literacy was a key factor in achieving these positive outcomes. The findings suggest the importance of ensuring equitable access to the Internet in efforts to improve educational and health outcomes for seasonal farmworkers and their families.
The knowledge of the brain processes underlying mental disorders has significantly increased during the last decades, but in spite of this very important research effort a biological marker is not ...available for such disorders. For example, neurophysiological techniques (EEG and MEG),have been broadly utilized in the investigation of the most important psychiatric syndromes such as schizophrenia, major depression, bipolar disorder or obsessive/compulsive disorder. The outcomes of some of those neurophysiological studies allowed the building of statistical models with very high sensitivity and specificity, although those models did not reach day-to-day clinical practice. A potential explanation for this situation is an inadequate analysis procedure which might be missing some important quantums of information contained in brain signals. In this vein, new methods of non-linear analysis have been proposed for the investigation of neurophysiological data. Particularly, the analysis of brain signals' complexity has been broadly utilized in the investigation of psychiatric disorders. Parameters of EEG-MEG complexity usually estimate the predictability of brain oscillations and/or the number of independent oscillators underlying the observed signals. More importantly, complexity parameters seem to be sensitive to the temporal components of brain activity, and therefore might reflect the dynamical nature of psychiatric disorders. This paper reviews some of the most relevant studies within this field, especially those focusing on the diagnosis, follow-up and prediction of response to treatment.
Thyroid disorders are clinically characterized by alterations of L-3,5,3',5'-tetraiodothyronine (T
), L-3,5,3'-triiodothyronine (T
), and/or thyroid-stimulating hormone (TSH) levels in the blood. The ...most frequent thyroid disorders are hypothyroidism, hyperthyroidism, and hypothyroxinemia. These conditions affect cell differentiation, function, and metabolism. It has been reported that 40% of the world's population suffers from some type of thyroid disorder and that several factors increase susceptibility to these diseases. Among them are iodine intake, environmental contamination, smoking, certain drugs, and genetic factors. Recently, the intestinal microbiota, composed of more than trillions of microbes, has emerged as a critical player in human health, and dysbiosis has been linked to thyroid diseases. The intestinal microbiota can affect host physiology by producing metabolites derived from dietary fiber, such as short-chain fatty acids (SCFAs). SCFAs have local actions in the intestine and can affect the central nervous system and immune system. Modulation of SCFAs-producing bacteria has also been connected to metabolic diseases, such as obesity and diabetes. In this review, we discuss how alterations in the production of SCFAs due to dysbiosis in patients could be related to thyroid disorders. The studies reviewed here may be of significant interest to endocrinology researchers and medical practitioners.
The prevalence of autism spectrum disorder (ASD) has significantly risen in the past three decades, prompting researchers to explore the potential contributions of environmental factors during ...pregnancy to ASD development. One such factor of interest is gestational hypothyroxinemia (HTX), a frequent condition in pregnancy associated with cognitive impairments in the offspring. While retrospective human studies have linked gestational HTX to autistic traits, the cellular and molecular mechanisms underlying the development of ASD-like phenotypes remain poorly understood. This study used a mouse model of gestational HTX to evaluate ASD-like phenotypes in the offspring.
To induce gestational HTX, pregnant mice were treated with 2-mercapto-1-methylimidazole (MMI), a thyroid hormones synthesis inhibitor, in the tap-drinking water from embryonic days (E) 10 to E14. A separate group received MMI along with a daily subcutaneous injection of T
, while the control group received regular tap water during the entire pregnancy. Female and male offspring underwent assessments for repetitive, anxious, and social behaviors from postnatal day (P) 55 to P64. On P65, mice were euthanized for the evaluation of ASD-related inflammatory markers in blood, spleen, and specific brain regions. Additionally, the expression of glutamatergic proteins (NLGN3 and HOMER1) was analyzed in the prefrontal cortex and hippocampus.
The HTX-offspring exhibited anxious-like behavior, a subordinate state, and impaired social interactions. Subsequently, both female and male HTX-offspring displayed elevated proinflammatory cytokines in blood, including IL-1β, IL-6, IL-17A, and TNF-α, while only males showed reduced levels of IL-10. The spleen of HTX-offspring of both sexes showed increased Th17/Treg ratio and M1-like macrophages. In the prefrontal cortex and hippocampus of male HTX-offspring, elevated levels of IL-17A and reduced IL-10 were observed, accompanied by increased expression of hippocampal NLGN3 and HOMER1. All these observations were compared to those observed in the Control-offspring. Notably, the supplementation with T
during the MMI treatment prevents the development of the observed phenotypes. Correlation analysis revealed an association between maternal T
levels and specific ASD-like outcomes.
This study validates human observations, demonstrating for the first time that gestational HTX induces ASD-like phenotypes in the offspring, highlighting the need of monitoring thyroid function during pregnancy.
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•CHI/PEC porous scaffolds have been employed as the host matrix to immobilize microporous MOFs.•The composite membrane fully retains the record AsIII and AsV adsorption capacity of ...the MOF.•There is a synergic function to photo-oxidize AsIII to AsV when assembling MOF and CHI/PEC in a composite membrane.•The multi-step mechanism for the dual AsIII to AsV oxidation and adsorption has been detailed.
The presence of arsenic as neutral arsenite and oxoanionic arsenate species are a worldwide issue that requires an effective remediation technology capable to remove both AsIII and AsV from water. In this research we propose the assembly of a membrane build up from chitosan/pectin (CHIPEC) composite biopolymer and the UiO-66-NH2 porous and photo-active metal–organic framework. CHIPEC@UiO-66-NH2 membrane integrates porosity, adsorptive capacity, and activity to photo-oxidize and adsorb AsIII and AsV species. Nanometric-sized UiO-66-NH2 was synthetized and homogeneously distributed within the CHIPEC matrix, achieving a composite membrane with optical physico-chemical and optical properties (band gap of 2.91 eV) suitable to be applied on photooxidation of AsIII and adsorption of AsV. Under optimal conditions, maximum adsorption capacities (Qmax) values of 254 and 168 mg g−1 were reached for AsIII adsorption by MOF and membrane, respectively. Notably, for AsV adsorption, Qmax values of 268 and 335 mg g−1 were reached for powdered and immobilized MOF, respectively. Moreover, the membrane keeps most of its activity for AsV adsorption when employed in surface and groundwater matrixes. Further, the efficiently of UiO-66-NH2 to photo-oxidize AsIII to AsV, subsequently adsorbing the arsenate oxyanions, is improved by a factor of five when is integrated into the polymer. A detailed multi-step mechanism for the arsenic transformation and adsorption in CHIPEC@UiO-66-NH2 has been proposed on the basis of the anionic exchange at Zr hexa-nuclear clusters and amino groups in the MOF. Overall, MOF-biopolymeric composite has been proved as a straightforward, efficient, low-cost, and environmentally friendly solution for detoxifying arsenic in surface and underground water.
There is increasing interest in the use of cannabis and its major non-intoxicating component cannabidiol (CBD) as a treatment for mental health and neurodevelopmental disorders, such as autism ...spectrum disorder (ASD). However, before launching large-scale clinical trials, a better understanding of the effects of CBD on brain would be desirable. Preclinical evidence suggests that one aspect of the polypharmacy of CBD is that it modulates brain excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) levels, including in brain regions linked to ASD, such as the basal ganglia (BG) and the dorsomedial prefrontal cortex (DMPFC). However, differences in glutamate and GABA pathways in ASD mean that the response to CBD in people with and without ASD may be not be the same. To test whether CBD 'shifts' glutamate and GABA levels; and to examine potential differences in this response in ASD, we used magnetic resonance spectroscopy (MRS) to measure glutamate (Glx = glutamate + glutamine) and GABA+ (GABA + macromolecules) levels in 34 healthy men (17 neurotypicals, 17 ASD). Data acquisition commenced 2 h (peak plasma levels) after a single oral dose of 600 mg CBD or placebo. Test sessions were at least 13 days apart. Across groups, CBD increased subcortical, but decreased cortical, Glx. Across regions, CBD increased GABA+ in controls, but decreased GABA+ in ASD; the group difference in change in GABA + in the DMPFC was significant. Thus, CBD modulates glutamate-GABA systems, but prefrontal-GABA systems respond differently in ASD. Our results do not speak to the efficacy of CBD. Future studies should examine the effects of chronic administration on brain and behaviour, and whether acute brain changes predict longer-term response.
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